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Biomedical subjects

T Iwaki

Publications and source records attributed to T Iwaki.

At least 163 records · Page 9Linked to original sources

Alpha B-crystallin in oxidative muscle fibers and its accumulation in ragged-red fibers: a comparative immunohistochemical and histochemical study in human skeletal muscle.

The alpha B-crystallin gene is abundantly expressed in the vertebrate lens and at lower levels in various non-lenticular tissues. Among the non-lenticular tissues, alpha B-crystallin is present at high levels in the heart and skeletal muscle. Using a specific antibody against alpha B-crystallin, the cellular localization of alpha B-crystallin was studied in biopsies of human skeletal muscles. Expression of alpha B-crystallin was observed in normal oxidative muscle fibers that show positive reactions for NADH-tetrazolium reductase and cytochrome c oxidase. In muscle diseases increased immunoreactivity for alpha B-crystallin was found in ragged-red fibers, which stained darkly with histochemistry for succinate dehydrogenase. Since alpha B-crystallin is related to small heat-shock proteins and can be induced by various stress conditions, the increased alpha B-crystallin immunoreactivity of ragged-red fibers could result from profound oxidative stress produced by the abnormal mitochondrial metabolism.

Adult↗

Widespread distribution of tau in the astrocytic elements of glial tumors.

Recently tau immunoreactivity has been observed in astrocytes in Alzheimer's disease and other neurological diseases. We examined the immunohistochemical localization of tau in 110 human brain tumors. Tau was widely distributed in the glial neoplastic cells and the reactive astrocytes in tumor tissues. In human surgical specimens positive immunostaining for tau was frequently observed in astrocytic tumors, oligodendroglial tumors, and glioblastoma, as well as neuronal tumors. The astrocytic neoplastic cells in medulloblastoma and other poorly differentiated tumors were also stained. In contrast, no immunoreactivity was observed in meningiomas and schwannomas. The expression of tau in brain tumors was mainly restricted to those cells with astrocytic features rather than small immature cells. The expression of tau mRNA was also demonstrated in astrocytic tumors. In conjunction with the findings of tau-positive astrocytes in some degenerative disorders, astrocytes are considered to have a potential to express tau through neoplastic transformation and reactive processes.

Animals↗

Detection of Epstein-Barr virus DNA in cardiac and aortic tissues from chronic, active Epstein-Barr virus infection associated with Kawasaki disease-like coronary artery aneurysms.

We describe three patients with chronic, active Epstein-Barr virus infection associated with Kawasaki disease-like coronary artery aneurysms. The Epstein-Barr virus genome was detected in three cardiac tissue samples and one aortic tissue sample examined by means of the polymerase chain reaction. These findings suggest that chronic Epstein-Barr virus infection may play a pathogenic role in the development of coronary artery aneurysms.

Antibodies, Viral↗

Quantitative structure-activity relationship (QSAR) study of elastase substrates and inhibitors.

One hundred Suc-X-Y-Ala-pNA peptides: (Suc: succinyl, pNA: p-nitroanilide, X, Y: Gly, Ala, Val, Leu, Ile, Phe, Pro, alpha-aminobutyric acid, norvaline, norleucine) were synthesized and their reaction constants with porcine pancreatic elastase (Km, kcat and kcat/Km) were determined. These reaction constants were quantitatively analyzed using the Free-Wilson/Fujita-Ban method. The contribution of amino acid side chains to the reaction constants Km, kcat and kcat/Km, expressed logarithmically, was found to be additive. On the other hand, 19 elastase inhibitors of the general formula CF3CO-X-Y-Ala-pNA (X,Y: ten amino acids) were synthesized, and their inhibition constants were compared with the Michaelis constant for the corresponding substrates and analyzed using free-energy-related substituent constants. In the analysis of amino acid side chains in the Y position, the Ki value of the inhibitor was generally correlated to the Km value of the substrate, which corresponded to the inhibitor, thus confirming the validity of the equation. log(1/Ki) = 1.271 log(1/Km) + 4.831 This study may serve as a prototypical approach to unraveling structure-activity relationships of peptide substrates and inhibitors of medicinal or agricultural importance.

Amino Acid Sequence↗

Alpha B-crystallin and 27-kd heat shock protein are regulated by stress conditions in the central nervous system and accumulate in Rosenthal fibers.

To understand the significance of the accumulation of alpha B-crystallin in Rosenthal fibers within astrocytes, the expression and metabolism of alpha B-crystallin in glioma cell lines were examined under the conditions of heat and oxidative stress. alpha B-crystallin mRNA was increased after both stresses, and alpha B-crystallin protein moved from a detergent-soluble to a detergent-insoluble form. In addition, Western blotting of Alexander's disease brain homogenates revealed that the 27-kd heat shock protein (HSP27), which is related to alpha B-crystallin, accumulates along with alpha B-crystallin. The presence of HSP27 in Rosenthal fibers was directly demonstrated by immunohistochemistry. Our results suggest that astrocytes in Alexander's disease may be involved in an as yet unknown kind of stress reaction that causes the accumulation of alpha B-crystallin and HSP27 and results in Rosenthal fiber formation.

Animals↗

Accumulation of alpha B-crystallin in brains of patients with Alexander's disease is not due to an abnormality of the 5'-flanking and coding sequence of the genomic DNA.

alpha B-Crystallin is a major protein component of Rosenthal fibers, which massively accumulate in the brains of patients suffering from Alexander's disease. To examine whether or not accumulation of alpha B-crystallin is due to any abnormality of the gene structures, we determined the sequence of the alpha B-crystallin gene in two cases of pathologically confirmed Alexander's disease. Direct sequencing of the promoter and coding regions of the alpha B-crystallin gene in patients revealed them to have a normal sequence. Northern blotting showed a single alpha B-crystallin mRNA species expressed in the Alexander's disease brain.

Aged↗

Creutzfeldt-Jakob disease with codon 129 polymorphism (valine): a comparative study of patients with codon 102 point mutation or without mutations.

We examined 7 patients with Creutzfeldt-Jakob disease (CJD) with a methionine-to-valine change at prion protein (PrP) codon 129 (CJD129 patients). These CJD129 patients did not have either a codon 117 or 198 point mutation. For comparison, we also examined 7 patients with Gerstmann-Sträussler syndrome (GSS) with a proline-to-leucine change at PrP codon 102 (GSS102 patients) and 13 patients without any known mutations at codons 102, 117, 129, 178, or 200 (CJDwild patients). CJD129 patients had a long clinical duration and ataxia at onset, but rarely had any periodic synchronous discharge in their electroencephalogram. Unlike CJDwild patients, all CJD129 patients have typical congophilic PrP plaques in their brain. These clinicopathological findings were similar to those of GSS102. However, the distribution and morphology of PrP deposits revealed by immunohistochemistry were different between CJD129 and GSS102. In GSS102 more numerous and various types of PrP plaques are seen throughout the brain, while in CJD129 patients a unicentric core was the major feature of PrP plaques. The change in codon 129 influences the clinical course and pathological findings in CJD.

Adult↗

Anaplastic large cell Ki-1 lymphoma in the central nervous system: report of an autopsy case.

A 45-year old immunocompetent man presented with multiple lesions in the brain. A histological examination of the tumors showed a diffuse infiltrate of lymphoid cells with cellular polymorphism and of multinucleated giant cells. These cells were immunolabeled with antibodies against B cell lineage and with a monoclonal antibody, Ber-H2 (CD30), which showed the presence of Ki-1 antigen. Recently, among systemic non-Hodgkin's lymphomas, attention has been given to Ki-1-positive lymphomas, which have been incorporated in the up-dated Kiel classification. We report here a case of Ki-1-positive lymphoma arising in the CNS and review previously reported cases.

Humans↗

Colocalization of prion protein and beta protein in the same amyloid plaques in patients with Gerstmann-Sträussler syndrome.

We examined paraffin-embedded brain sections from three patients with Creutzfeldt-Jakob disease (CJD) and four patients with Gerstmann-Sträussler syndrome (GSS) who also had beta protein deposits in the brains. Immunostaining using anti-prion protein (PrP) and anti-beta protein coupled with formic acid pretreatment, revealed PrP deposits and beta protein deposits, respectively. In all four GSS patients examined, sequential double immunostaining and single immunostaining in serial sections or simultaneous double immunofluorescence revealed the colocalization of PrP and beta protein in the same amyloid plaques. The plaques labeled with both antibodies were designated as beta-PrP plaques. Small kuru plaques of less than 15 microns in diameter were rarely found to coexist with beta deposits. The percentages of beta-PrP plaques in larger kuru plaques were not constant among the four GSS patients. The colocalization patterns of both deposits were observed as being roughly of two types as follows: (1) diffuse beta protein deposits located around the PrP core; and (2) a beta protein core and PrP core simultaneously existing in one amyloid plaque. Under an electron microscope, we were able to confirm the presence of both beta protein and PrP in a single plaque in four GSS patients older than 60 years old. In contrast, no colocalization of either deposits was seen in the amyloid plaque core fractions of a young GSS patient who had no beta protein deposits, even at the electron microscopic level. Therefore, the colocalization of both proteins in a single plaque is believed to be age-related and incidental in GSS patients but suggests a similar morphogenesis of both amyloid deposits.

Adult↗

A fluorescent molecular rotor probes the kinetic process of degranulation of mast cells.

A confocal fluorescence microscope was used to study the exocytotic secretory processes of mast cells in combination with an fluorescent molecular rotor, 9-(dicyanovinyl)julolidine (DCVJ). DCVJ is known to be an unique fluorescent dye which increases its quantum yield with decreasing intramolecular rotation. Here, DCVJ-loaded peritoneal rat mast cells were stimulated with compound 48/80 and their fluorescence images were compared with fluorescence calcium images of fluo-3-loaded mast cells. Subsequent to transient increases in intracellular free calcium ion concentration, DCVJ fluorescence increased dramatically in the cytoplasm and formed a ring-like structure around the nucleus, suggesting the possibility that the dye bound to the proteins composing the cytoskeletal architecture. Furthermore, the increases of DCVJ fluorescence intensities were mostly blocked in the presence of cytochalasin D (10 microM). However, fluo-3 fluorescence intensities still increased after addition of compound 48/80.

Aniline Compounds↗

Effects of L-NMMA and L-NNA on the selective ATP-induced enhancement of intratumoral blood flow.

We studied the effects of NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine (L-NNA) on the selective ATP and adenosine-induced enhancement of intratumoral blood flow in rats measured by the hydrogen clearance method. Both adenosine and ATP produced a selective enhancement of the intratumoral blood flow. Neither L-NMMA nor L-NNA had a significant effect on either the CBF or the intratumoral blood flow. Adenosine-induced enhancement was not inhibited by L-NMMA or L-NNA. On the other hand, the ATP-induced enhancement was totally inhibited by both L-NMMA and L-NNA. The inhibitory action of L-NMMA against ATP was blocked by L-arginine, but not by D-arginine. It is suggested that the ATP-induced increase of intratumoral blood flow is evoked by nitric oxide synthesized from the endothelium of the intratumoral blood vessels.

Adenosine↗

Massive accumulation of modified tau and severe depletion of normal tau characterize the cerebral cortex and white matter of Alzheimer's disease. Demonstration using the hydrated autoclaving method.

Using the hydrated autoclaving method, a new immunohistochemical procedure to enhance tau immunoreactivity in formalin-fixed brain tissue, the authors recently reported that tau protein is detected in neuronal cell bodies and proximal dendrites, gray matter neuropil, axons, and glial cells in normal human hippocampus and neocortex. In the this study, the authors performed a comparative study of the distribution of normal and modified forms of tau in Alzheimer's disease (AD) and control brains. In the cerebral cortex and white matter of AD brains, a massive accumulation of modified tau and/or severe depletion of normal tau were documented in all the tau compartments. In mild AD cases, gray matter neuropil, axons, and glial cells were less severely involved than neuronal perikarya. In the controls, neuronal perikarya were often involved by modified tau accumulation, but the other compartments showed normal distribution. These observations suggest that modifications of tau which lead to neurofibrillary lesions in AD may begin in neuronal perikarya and extend to the other tau compartments in advanced stages of the disease.

Adult↗

[Effect of prostaglandin E1 on peripheral body temperature in pediatric patients after open heart surgery].

The effect of prostaglandin E1 was studied to examine if it works favorably for peripheral circulation in pediatric patients after cardiac surgery. Dose of 0.1 mcg.kg-1.min-1 increased temperature of dorsal pedis significantly. Difference of temperature of dorsalis pedis and that of rectum was significantly smaller than that in control group. A significant increase in heart rate and a decrease in systolic arterial pressure produced no clinical side effects. We conclude that prostaglandin E1 is a useful and safe vasodilator for circulatory management of pediatric patients after cardiac surgery.

Age Factors↗

Lectin histochemistry of human fetal notochord, ecchordosis physaliphora, and chordomas.

Lectin histochemical studies of human fetal notochord, ecchordosis physaliphora, and eight chordomas were performed. Ecchordosis physaliphora and eight chordomas were stained with Ricinus communis type I, Canavalia ensiformis, Triticum vulgaris, and Limax flavus. Ricinus communis type I, T vulgaris, and L flavus reacted with both tumor cells and the extracellular mucinous matrix, while C ensiformis mainly reacted with the cytoplasm of tumor cells. Thus, tumor cells were most recognizable with the C ensiformis stain. After neuraminidase treatment, ecchordosis physaliphora and chordomas invariably showed positivities for Arachis hypogaea. The lectin-binding patterns of chordomas closely reflected those of the human fetal notochord. Chordomas were completely sialylated regardless of either the clinical course or histopathological findings. Among the eight lectins, C ensiformis heavily labeled chordoma cells but not extracellular space. This was probably because asparagine-linked N-glycosylation was active in the chordomas, while the high-mannose-type oligosaccharides were apt to remain in the cytoplasm.

Adult↗

Accumulation of alpha B-crystallin in central nervous system glia and neurons in pathologic conditions.

Alpha B-crystallin, a major protein of the vertebrate lens, is found in the central nervous system (CNS) and is a major protein component of Rosenthal fibers (RF), intracytoplasmic inclusions within astrocytes. Its level of expression in the normal CNS is low and appears to be confined to glial cells, both astrocytes and oligodendrocytes. A number of human brains displaying a variety of pathologic changes were examined by immunohistochemistry with an anti-alpha B-crystallin antiserum and increased immunoreactivity was found in astrocytes and oligodendrocytes without the formation of RFs. Furthermore, some neurons in neurodegenerative disorders were also immunolabeled with the anti-alpha B-crystallin antiserum. Thus, the accumulation of alpha B-crystallin appears to be part of the repertoire of reactive processes of CNS glial cells and some neurons in pathologic conditions.

Animals↗

Preferential expression of alpha B-crystallin in astrocytic elements of neuroectodermal tumors.

Recently the authors have identified a major component of Rosenthal fibers as alpha B-crystallin, a major lens protein. In the current study the authors investigated the expression of alpha B-crystallin in four cultured glioma cell lines and in 115 human neuroectodermal tumors. alpha B-crystallin was expressed differentially by those glioma cell lines, but not by neuroblastoma cell lines. Northern blot analysis revealed two distinct messages for alpha B-crystallin in C-6, whereas only a single message in U-373MG and G26-24. In human surgical specimens positive immunostaining was frequently observed in the following brain tumors: pilocytic astrocytoma of the juvenile type, anaplastic astrocytoma, glioblastoma multiforme, and subependymal giant cell astrocytoma. The astrocytic elements of mixed oligoastrocytomas, glioblastomas with sarcomatous components, and gangliogliomas were likewise strongly stained. In contrast, little immunoreactivity was observed in ependymal and choroid plexus tumors. Thus, alpha B-crystallin is mainly expressed by astrocytic tumors among neuroectodermal neoplasms, without regard to the presence of Rosenthal fibers.

Blotting, Northern↗

Comprehensive lectin histochemistry of normal and neoplastic human choroid plexus cells: alternation of lectin-binding patterns through neoplastic transformation.

Lectin histochemistry of the normal and neoplastic human choroid plexus cells [six choroid plexus papillomas (CPPs) and three choroid plexus carcinomas (CPCs)] was performed using eight representative lectins to study the development of sugar chain structures and also to determine whether lectins were useful for a histopathological diagnosis of choroid plexus neoplasms (CPNs). The normal choroid plexus cells reacted with Ricinus communis (RCA-I). Canavalia ensiformis (Con A), Limax flavus (LFA) and Triticum vulgaris (WGA), while Arachis hypoaea (PNA) stained them only after the removal of sialic acid. Human fetal choroid plexus cells at 8 weeks gestation already showed the same lectin-binding patterns as adult ones. All CPNs were stained by RCA-I and Con A in a similar manner as the normal choroid plexus cells. Although seven CPNs were positive for LFA, two CPCs were not stained by LFA, which bound to sialic acid. Two LFA-positive CPPs were stained by PNA before the removal of sialic acid. Moreover, unlike the normal choroid plexus cells, Ulex europaeus-, Glycine maximus- and Dolichos biflorus-binding sites often appeared, and WGA-binding sites of three CPNs remained even after sialic acid removal. In conclusion, the glycosialylation in normal choroid plexus cells was completed during the early embryonic stage. The lectin-binding patterns of CPNs were heterogenous in each case. The alternation of the glycosialylation and/or acquisition of binding sites for some lectins was sometimes observed through a neoplastic transformation.

Adult↗

Expression of alpha B-crystallin in the developing rat kidney.

The expression and cellular localization of alpha B-crystallin during rat renal development was studied by Northern blot analysis and by immunocytochemistry. Northern blotting of total RNA extracted from whole kidneys revealed that the messenger RNA for alpha B-crystallin rapidly increased after birth to reach adult levels by 20 days. At the same time, immunohistochemistry for alpha B-crystallin demonstrated that the prominent elongation of Henle's loop during the first 10 days of life was accompanied by increased alpha B-crystallin expression. Thus, the development of alpha B-crystallin expression is correlated temporally with the acquisition of tubule function in early post-natal life.

Animals↗